Is QRFPR p.Val183Met (c.547G>A) pathogenic?

QRFPR p.Val183Met (c.547G>A) is classified Uncertain significance in QRFPR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.3319); Rare (popmax 0.167%, sas).

How common is QRFPR p.Val183Met (c.547G>A) in the general population?

QRFPR p.Val183Met (c.547G>A) is rare (popmax 0.167%, sas) (gnomAD).

What do computational predictors say about QRFPR p.Val183Met (c.547G>A)?

AlphaMissense predicts likely benign (score 0.3319) — an in-silico prediction, not a clinical call.

QRFPR p.Val183Met

c.547G>A · VCV3941510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3319 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3319	likely benign
REVEL	0.488	indeterminate
SaProt	LLR -9.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 51 kb · p 0.68 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% South Asian · 152/91,072 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.0104% 168/1,613,676 alleles · rare exomes 158/1,461,360 · genomes 10/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.167%	599
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00446%	22,436
African / African-American	0.004%	25,007
European (non-Finnish)	0.000678%	147,447

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: QRFPR
Protein: p.Val183Met
Coding: c.547G>A
MANE Select: NM_198179
Type: single nucleotide variant
Location: chr4:121336821 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.74 · 2 PDB
Residue 183: an α-helix

Full QRFPR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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QRFPR p.Ala128Thr Uncertain significance ★ ⚠ same type
QRFPR p.Ala315Val Uncertain significance ★ ⚠ same type
QRFPR p.Arg13Trp Uncertain significance ★ ⚠ same type
QRFPR p.Arg160Gln Uncertain significance ★ ⚠ same type
QRFPR p.Arg161Thr Uncertain significance ★ ⚠ same type
QRFPR p.Arg16Pro Uncertain significance ★ same type
QRFPR p.Arg22Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/qrfpr-p-val183met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown